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Title: Steroid receptor coactivator-1 mediates estrogenic actions to prevent body weight gain in female mice

Author
item ZHU, LIANGRU - Children'S Nutrition Research Center (CNRC)
item YANG, YOUNGJIE - Children'S Nutrition Research Center (CNRC)
item XU, PINGWEN - Children'S Nutrition Research Center (CNRC)
item ZOU, FANG - Children'S Nutrition Research Center (CNRC)
item YAN, XIAOFENG - Children'S Nutrition Research Center (CNRC)
item LIAO, LAN - Baylor College Of Medicine
item XU, JIANMING - Baylor College Of Medicine
item O'MALLEY, BERT - Baylor College Of Medicine
item XU, YONG - Children'S Nutrition Research Center (CNRC)

Submitted to: Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/9/2012
Publication Date: 1/1/2013
Citation: Zhu, L., Yang, Y., Xu, P., Zou, F., Yan, X., Liao, L., Xu, J., O'Malley, B.W., Xu, Y. 2013. Steroid receptor coactivator-1 mediates estrogenic actions to prevent body weight gain in female mice. Endocrinology. 154(1):150-158.

Interpretive Summary: In this work, we demonstrated that the female sex hormone, estrogen, acts in the hypothalamus (a brain structure), to prevent body weight gain in female animals. In particular, we found that the anti-obesity effects of the hormone requires the functions of a protein, namely steroid receptor co-activator-1. The results provide new sights regarding how the female sex hormone acts to produce metabolic benefits, and may facilitate development of novel therapies for obesity, especially for post-menopausal women.

Technical Abstract: Estrogen receptor-alpha (ERalpha) expressed by hypothalamic proopiomelanocortin and steroidogenic factor-1 neurons largely mediates the antiobesity effects of estrogens in females. However, the critical molecular events that are coupled to ERalpha and mediate estrogenic effects on energy balance remain unknown. In the current study, we demonstrated that steroid receptor coactivator-1 (SRC1), a nuclear receptor coactivator, is abundantly expressed by both proopiomelanocortin and steroidogenic factor-1 neurons. We further showed that central administration of an ERalpha agonist, propyl pyrazole triol, acutely increases physical interaction between SRC1 and ERalpha in the hypothalamus. Finally, we demonstrated that the effects of estrogens on energy homeostasis are significantly blunted in female mice lacking SRC1 globally. Collectively our results indicate that SRC1 is functionally required to mediate the antiobesity effects of estrogen-ERalpha signals.